PHRM1102 W7 Workshop
Sonia would like to know whether a non-steroidal anti-inflammatory drug, such as ibuprofen or diclofenac, would be more effective for her knee pain compared to paracetamol.
In PICO form:
| PICO | Details |
|---|---|
| Participants | People with knee osteoarthritis |
| Intervention | Non-steroidal antiinflammatory drugs |
| Comparator | Paracetamol |
| Outcome | Pain self-report and/or assessments of functional ability in osteoarthritis |
Arrange the names of your group into alphabetical order.
The first two students need to search Pubmed for randomized trials that answer the question
The second two students need to search Pubmed for systematic reviews that answer the question
The third two students need to use either DynaMed or UptoDate to answer the question
If your group is larger than 6, any remaining students can take their pick from the options above
Which was the first treatment to show mortality benefit in Covid-19?
How was this demonstrated?
You look after a residential aged care facility. They have just notified that they will receive a shipment of a Covid-19 antiviral, molnupiravir.
They ask you
What are some of the challenges of demonstrating drug harms?
| Participants | Patients with rheumatoid arthritis who were expected to require NSAIDs for at least a year |
| Intervention | Rofecoxib 50 mg once daily |
| Comparator | Naproxen 500 mg twice daily |
| Outcome | Confirmed clinical upper gastrointestinal event |
During a median follow-up of 9.0 months, 2.1 confirmed gastrointestinal events per 100 patient-years occurred with rofecoxib, as compared with 4.5 per 100 patient-years with naproxen (relative risk, 0.5; 95% confidence interval 0.3 to 0.6; P < 0.001).
The incidence of myocardial infarction was lower among patients in the naproxen group than among those in the rofecoxib group (0.1 percent vs. 0.4 percent; relative risk, 0.2; 95 percent confidence interval, 0.1 to 0.7); the overall mortality rate and the rate of death from cardiovascular causes were similar in the two groups.
| Participants | Patients with a history of colorectal adenomas |
| Intervention | Rofecoxib 25 mg daily |
| Comparator | Placebo |
| Outcome | Recurrent neoplastic polyps of the large bowel |
A total of 46 patients in the rofecoxib group had a confirmed thrombotic event during 3059 patient-years of follow-up (1.50 events per 100 patient-years), as compared with 26 patients in the placebo group during 3327 patient-years of follow-up (0.78 event per 100 patient-years); the corresponding relative risk was 1.92 (95 percent confidence interval, 1.19 to 3.11; P=0.008).
| Participants | Patients with rheumatoid arthritis or osteoarthritis and expected to need continuous treatment with a NSAID |
| Intervention | Celecoxib 400 mg twice a day |
| Comparator | Ibuprofen 800 mg three times a day or diclofenac 75 mg twice a day |
| Outcome | Symptomatic upper GI ulcers or ulcer complications |
For all patients, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.76% vs 1.45% (P = .09) and 2.08% vs 3.54% (P= .02), respectively.
Juni et al. (2002) highlights that the original protocols were for two studies, one comparing celecoxib with diclofenac and the other with ibuprofen.
The original protocol describes the studies continuing for 12 and 15 months respectively, and uses a more stringent FDA-specified criteria for judging ulcer-related complications.
When the data is analysed as planned there is no difference between celecoxib, ibuprofen and diclofenac
Provide the study PICO
If relevant, calculate the RR, RRR, ARR and NNT
| Participants | Nonhospitalised, unvaccinated adults with mild-to-moderate lab-confirmed Covid-19 and at least one risk factor for severe illness of less than 5 days |
| Intervention | Molnupiravir 800 mg twice daily for 5 days |
| Comparator | Placebo |
| Outcome | Incidence of hospitalisation or death at day 29 |
In the analysis of all participants who had undergone randomization, the percentage of participants who were hospitalized or died through day 29 was lower in the molnupiravir group than in the placebo group (6.8% [48 of 709] vs. 9.7% [68 of 699]; difference, −3.0 percentage points; 95% CI, −5.9 to −0.1).
| Endpoint | No endpoint | Total | |
|---|---|---|---|
| Treatment | 48 | 661 | 709 |
| Control | 68 | 631 | 699 |
Comment on the relevance of these findings for residents in a aged care facility.
Bombardier, C., Laine, L., Reicin, A., Shapiro, D., Burgos-Vargos, R., Davis, B., & al, et. (2000). Comparision of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis: VIGOR study group. New England Journal of Medicine, 343, 1520–1528.
Bresalier, R. S., Sandler, R. S., Quan, H., Bolognese, J. A., Oxenius, B., Horgan, K., Lines, C., Riddell, R., Morton, D., Lanas, A., Konstam, M. A., & Baron, J. A. (2005). Cardiovascular events associated with Rofecoxib in a colorectal andenoma chemoprevention trial. New England Journal of Medicine, 352(11), 1092–1102.
Jayk Bernal, A., Gomes da Silva, M. M., Musungaie, D. B., Kovalchuk, E., Gonzalez, A., Delos Reyes, V., MartÃn-Quirós, A., Caraco, Y., Williams-Diaz, A., Brown, M. L., Du, J., Pedley, A., Assaid, C., Strizki, J., Grobler, J. A., Shamsuddin, H. H., Tipping, R., Wan, H., Paschke, A., … De Anda, C. (2022). Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients. New England Journal of Medicine, 386(6), 509–520. https://doi.org/10.1056/NEJMoa2116044
Juni, P., Rutjes, A. W. S., & Dieppe, P. A. (2002). Are selective COX 2 inhibitors superior to traditional non steroidal anti-inflammatory drugs? BMJ (Clinical Research Ed), 324(7349), 1287–1288. http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=12039807&retmode=ref&cmd=prlinks
Silverstein, F. E., Gaich, G., Goldstein, J. L., Simon, L. S., Pincus, T., Whelton, A., Makuch, R., Eisen, G., Agrawal, N. M., Stenson, W. F., Burr, A. M., Zhao, W. W., Kent, J. D., Lefkowith, B., Verburg, K. M., & Geis, G. S. (2000). Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: The CLASS study: A Randomzed Controlled Trial. JAMA: The Journal of the American Medical Association, 284(1247-55).